Nuclear magnetic resonance studies on the antibiotic avoparcin, Conformational properties in relation to...

Avoparcin is a commercially important glycopeptide antibiotic which is active against Gram-positive bacteria. Recently, beta-avoparcin, the major component of the avoparcin mixture, and several other analogues have been structurally characterized and tested for their antibacterial activity. Varying degrees of activity were observed for only minor structural differences. For example, beta-avoparcin and epi-beta-avoparcin, which differ only in the stereochemistry at position 1' of the NH2-terminal phenylsarcosine subunit, exhibit a 10- to 100-fold difference in antibacterial activity. Following the supposition that the conformational properties of these molecules may explain the differences in their antibacterial activity, we have analyzed the conformations of beta-avoparcin, epi-beta-avoparcin, and other avoparcin analogues in aqueous solutions using NMR methods. On the basis of an analysis of the 1H chemical shifts, 1H-1H nuclear Overhauser enhancement data, and pH titration experiments, it was concluded that the conformations of all of the analogues are similar at the COOH terminus. However, for beta-avoparcin and epi-beta-avoparcin, conformational differences were observed in the NH2-terminal region of the molecules. In this paper, we present a detailed description of the over-all conformations of these two glycopeptides as deduced from an in-depth analysis of their corresponding 1H NMR spectra and discuss the possible relationships this may have with their markedly different antibacterial activities.